The primary mission of the Hematologic Malignancies Program (HEM) is to improve our understanding ofthe molecular pathogenesis, diagnosis, and treatment of leukemia and lymphoma. Examination of the differences between neoplastic cells and their normal counterparts has provided insight into the molecular and biochemical features that define the malignant phenotype. In addition, research on genetic and epigenetic alterations within premalignant and malignant lesions has provided a blueprint ofthe molecular signatures that contribute to disease development and progression. Together with research on biochemical factors that govern cell-cycle progression, cellular differentiation, response to injury, self-renewal and programmed cell death, investigators are working to identify molecular pathways and/or leukemia-associated antigens that could be targeted by antineoplastic drugs and/or immune therapy. The program is organized into four themes: identification of mutations from primary tumor samples; validation of signaling pathways using tissue culture and animal models; preclinical testing of novel therapeutic strategies, Phase l/ll clinical trials of novel therapeutics with associated correlative studies. The HEM Program has 32 members from 6 academic departments with $12.7 Million of peer review research grant funding (annual direct costs), including $2.7 Million from NCI. Members of the HEM Program published 438 programmatically aligned articles (2007-2012); 16% were the result of intraprogrammatic collaborations, 14% were interprogrammatic.